Overview: Clostridium tetani
is a Gram-positive, spore-forming, rod-shaped
bacterium that is resistant to temperature
modifications, moisture, and chemical
disinfectants. C. tetani is strictly anaerobic
and dies in the presence of oxygen; however,
spores produced by this species are able to
withstand oxygenated environments and other
harmful environments. The endospores are
produced in a swollen sporangium and their shape
generally resembles a 'drumstick' (Figure 1). Under
anaerobic conditions, C. tetani
spores geminate and produce exotoxins, namely,
tetanospasmin (tetanus neurotoxin, abbreviated
TeNT) and tetanolysin. The genes
encoding these toxins are located on separate
plasmids within the bacterium.

Figure 1. Clostridium tetani endospores in a
swollen sporangium.

Virulence
and Pathogenicity: Tetanus
toxin is the neurotoxin produced by the
vegetative cell of C. tetani
when spores germinate under anaerobic conditions
in an open wound, causing tetanus. The toxin has
no known function for clostridia (sulfite-reducing
bacteria) in the soil
environment where they are normally encountered.

Tetanus toxin spreads through tissue spaces into
the lymphatic and vascular systems. It enters
the nervous system at the neuromuscular
junctions and migrates through nerve trunks and
into the central nervous system by
retrograde axonal
transport. The protein tetanus toxin has a
molecular weight of 150 kDa (kiloDaltons). It is
made up of two parts, namely, a 100 kDa heavy or
B-chain and a 50 kDa light or A-chain. The
chains are connected by a disulfide bond. The
B-chain binds to cell surface
disialogangliosides (GD2 and GD1b) on the
neuronal membrane. The A-chain, a zinc-based
endopeptidase,
attacks the vesicle-associated membrane protein.

The action of the A-chain
stops the affected neurons from releasing the
inhibitory neurotransmitters GABA (gamma
aminobutyric acid) and glycine by degrading the
protein synaptobrevin, a small integral
protein of secretory vesicles. This results in a
failure to inhibit motor reflexes from the
smallest stimulus, which causes life-threatening
muscle spasms, termed a tetanic spasm.
Similarly, neonatal tetanus occurs in infants
born without protective passive immunity,
because the mother is not immune. It usually
occurs through infection of the unhealed
umbilical stump, particularly when the stump is
cut with an unsterile instrument (Figure 2).

Figure 2.
This neonate is displaying a bodily rigidity
produced by Clostridium tetani
exotoxin, called neonatal tetanus.

Tetanolysin
directs the multiplication of the
bacteria, which is also associated with
tetanus (Atriham and Crown, 2007). The
exotoxin belongs to a family of protein toxins
known as cytolysins which bind to
cholesterol. Cytolysins form pores in the
cytoplasmic membrane that allows for the passage
of ions and other molecules into the cell. The
molecular weight of tetanolysin is approximately
55 kDA.

Diagnosis: Diagnosis of C. tetani is based on clinical features rather than
laboratory verification. Most
tetanus infections are results of small
punctures to the skin that become infected with
C. tetani spores. Some of
the symptoms of tetanus include
hypertonia and
generalized muscle spasms, in absence of other
noticeable medical causes.

Figure 2. Sir
Charles Bell's portrait of a soldier dying of
tetanus. The characteristic rigidity of the body
is referred to as opisthotonos and risus
sardonicus.

Risk Factors:
Race, sex, and age have some associations with
tetanus. In fact, the highest incidence of tetanus was
found in Hispanics, followed by whites and then
African Americans. Also, men are believed to be better protected
against tetanus than women, due to additional
vaccination for reasons such as military and
professional needs. Finally, the incidence of
tetanus increases as people age.

Infection caused by C. tetani can
originate from puncture
wounds (stepping on a nail), cuts and scrapes,
and intramuscular injections.
People who have frostbites, dental infections,
penetrating eye injuries, and umbilical stump
infections are more susceptible to tetanus, as
are people with diabetes, chronic wounds,
parental drug abuse, and recent surgery. It is important to note that
correlation is not causation,
meaning that those who have diabetes, for
instance, are not in any way more susceptible to
infection than a healthy individual.

C. tetani
spores can be found in soil, dust, animal
intestines and human feces. Generally, humans are
not carriers of this pathogen; thus, carrier rates are
low and range between 0 and 25%.
Likewise, this organism is not a regular member of the
human intestinal flora and only passes
through depending on ingestion.

Immunity and
Vaccination: Treatment of tetanus
includes treating wounds and managing the pain
caused by the symptoms and complications due to
tetanus. Anti-tetanus immunoglobulin and
antibiotics should be given immediately and may
be beneficial in stopping progression of the
infection. Contracting the tetanus
disease does not cause immunity. The amount of
the tetanus toxin is not high enough to induce
an immune response to it; therefore,
vaccinations for tetanus are required.
Administration of inactivated tetanus toxin,
also known as a toxoid, induces antibody
responses in hosts and stops C. tetani
from causing tetanus (Casadevall and Pirofski,
1999). Injections of tetanus toxoid are given at
various stages throughout life.
Three injections are given to babies in their
first year; a booster is given one year later
and another booster is given when children begin
school. Even if immunized, people who sustain a
dangerous wound should be given a tetanus toxoid
injection.